Open AccessCSF1R methylation is a key regulatory mechanism of tumor‑associated macrophages in hepatocellular carcinoma
Author(s) -
Bin Cui,
Xiaohui Fan,
Daizhan Zhou,
Liangmei He,
Yirun Li,
Dandan Li,
Hui Lin
Publication year - 2020
Publication title -
oncology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.766
H-Index - 54
eISSN - 1792-1082
pISSN - 1792-1074
DOI - 10.3892/ol.2020.11726
Subject(s) - methylation , hepatocellular carcinoma , dna methylation , biology , oncogene , cancer , cancer research , metastasis , carcinoma , immunohistochemistry , pathology , cell cycle , medicine , gene expression , immunology , gene , biochemistry , genetics
Tumor-associated macrophages (TAMs) are important in tumor microenvironments and are closely associated with cancer occurrence, metastasis and progression. Colony stimulating factor 1 receptor (CSF1R) serves a crucial role in TAM formation. Whether CSF1R expression is regulated by DNA methylation in hepatocellular carcinoma (HCC) has not been fully elucidated. In the current study, HCC and adjacent non-cancerous tissue (ANT) samples were collected from 160 patients with HCC. CSF1R methylation levels were analyzed using a Mass ARRAY Analyzer to establish the potential impact of CSF1R methylation alternations on HCC clinicopathological characteristics. The mean methylation level of the CSF1R promoter (chr 5:149492491-149492958) was demonstrated to be significantly higher in ANTs compared with HCC tissues (65.3±7.5% vs. 57.3±14.4%, respectively; P<0.0001). CSF1R also exhibited decreased expression in HCC tissues compared with ANTs (P=0.0026). However, CSF1R expression was negatively correlated with CSF1R methylation levels in ANTs (r>0.4; P<0.0001). Further analysis indicated that patients with diabetes exhibited lower methylation levels in ANTs compared with HCC tissues (P=0.0062). Furthermore, CSF1R hypomethylation in ANTs was associated with a larger number of tumors (P=0.0332), larger tumor size (P=0.0494) and higher tumor grade (P=0.0244). Therefore, methylation alternation of the CSF1R promoter region analyzed in the present study was a key regulatory mechanism on CSF1R expression and ANT hypomethylation indicated poor clinicopathological characteristics of HCC. CSF1R may be a potential immunological therapeutic target for HCC.